The genetic markers of the variable regions of rabbit antibodies will be used to study genetic control of antibody biosynthesis. The markers used in this study will be the group a allotypes for the VH region and the idiotypic determinants for the binding site. Amino terminal sequence variations will serve as markers for the VL regions in this study. Observations of antibodies with identical idiotypes, but differing in other V region markers, have suggested that multiple genes may interact prior to synthesis of these polypeptide chains. This idea is supported by data from other systems, such as the human myeloma proteins. Antibodies with informative combinations of variable region markers will be identified and characterized serologically and structurally in an attempt to further define the genetic system that gives rise to V regions. Subspecificities of the group a (VH allotypes) of the rabbit have been observed in studies on homogeneous antibodies. Possible explanations for these subspecificities include: 1) each group a allele includes a number of structural variants; or 2) diverse expression of the allotype is caused by modulation of the allotypic specificities by amino acid differences in the binding site components. These possibilities will be explained by structural and serological studies on homogeneous antibodies with different allotypic subspecificities.